In vitro biotransformations of isocupressic acid by cow rumen preparations: formation of agathic and dihydroagathic acids.
Isocupressic acid [15-hydroxylabda-8(17),13E-dien-19-oic acid] (1) was incubated under anaerobic conditions for 48 h in an in vitro ruminal fluid mixture and was transformed into two metabolites. The two metabolites were identified by GC/MS as agathic acid [labda-8(17),13(E)-diene-15,19-dioic acid] (4E) and dihydroagathic acid [labda-8(17)-ene-15,19-dioic acid] (6). Metabolite identities were confirmed by chemical conversions of isocupressic acid (1) and imbricataloic acid (5) into 4E and 6, respectively. Structures of synthetic metabolites were confirmed by 1H and 13C NMR, specific rotation, GC/MS, and high-resolution mass spectrometry. Plasma obtained from cows that were fed Ponderosa pine needles contained (13R,S)-dihydroagathic acid (6) but not isocupressic acid (1) or 4E. The results suggest that isocupressic acid (1) is metabolically oxidized to agathic acid (4E), subsequently reduced to (13R,S)-dihydroagathic acid (6) in the rumen, and then absorbed into the bloodstream of cattle.
Lin
S J
SJ
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242, USA.
Short
R E
RE
Ford
S P
SP
Grings
E E
EE
Rosazza
J P
JP
D000693:Anaerobiosis; D000821:Animal Feed; D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism*; D002417:Cattle; D003998:Dicarboxylic Acids / Q000378:metabolism*; D004224:Diterpenes; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D012417:Rumen / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism*
D002264:Carboxylic Acids; D003998:Dicarboxylic Acids; D004224:Diterpenes; D013764:Tetrahydronaphthalenes; C110793:isocupressic acid; C110794:dihydroagathic acid; C110795:agathic acid